BOSTON - March 25, 2008 - Low doses of the toxic gas responsible
for the unpleasant odor of rotten eggs can safely and reversibly
depress both metabolism and aspects of cardiovascular function in
mice, producing a suspended-animation-like state. In the April 2008
issue of the journal Anesthesiology, Massachusetts General
Hospital (MGH) reseachers report that effects seen in earlier studies
of hydrogen sulfide do not depend on a reduction in body temperature
and include a substantial decrease in heart rate without a drop
in blood pressure.

"Hydrogen sulfide is the stinky gas that can kill workers
who encounter it in sewers; but when adminstered to mice in small,
controlled doses, within minutes it produces what appears to be
totally reversible metabolic suppression," says Warren Zapol,
MD, chief of Anesthesia
and Critical Care at MGH and senior author of the Anesthesiology
study. "This is as close to instant suspended animation as
you can get, and the preservation of cardiac contraction, blood
pressure and organ perfusion is remarkable."

Previous investigations into the effects of low-dose hydrogen sulfide
showed that the gas could lower body temperature and metabolic rate
and also improved survival of mice whose oxygen supply had been
restricted. But since hypothermia itself cuts metabolic needs, it
was unclear whether the reduced body temperature was responsible
for the other observed effects. The current study was designed to
investigate both that question and the effects of hydrogen sulfide
inhalation on the cardiovascular system.

The researchers measured factors such as heart rate, blood pressure,
body temperature, respiration and physical activity in normal mice
exposed to low-dose (80 ppm) hydrogen sulfide for several hours.
They analyzed cardiac function with electrocardiograms and echocardiography
and measured blood gas levels. While some mice were studied at room
temperature, others were kept in a warm environment - about 98º
F - to prevent their body temperatures from dropping.

In all the mice, metabolic measurements such as consumption of
oxygen and production of carbon dioxide dropped in as little as
10 minutes after they began inhaling hydrogen sulfide, remained
low as long as the gas was administered, and returned to normal
within 30 minutes of the resumption of a normal air supply. The
animals' heart rate dropped nearly 50 percent during hydrogen sulfide
adminstration, but there was no significant change in blood pressure
or the strength of the heart beat. While respiration rate also decreased,
there were no changes in blood oxygen levels, suggesting that vital
organs were not at risk of oxygen starvation.

The mice kept at room temperature had the same drop in body temperature
seen in earlier studies, but those in the warm environment maintained
normal body temperatures. The same metabolic and cardiovascular
changes were seen in both groups, indicating that they did not depend
on the reduced body temperature, and analyzing the timing of those
changes showed that metabolic reduction actually began before body
temperature dropped.

"Producing a reversible hypometabolic state could allow organ
function to be preserved when oxygen supply is limited, such as
after a traumatic injury," says Gian Paolo Volpato, MD, MGH
Anesthesiology research fellow and lead author of the study. "We
don't know yet if these results will be transferable to humans,
so our next step will be to study the use of hydrogen sulfide in
larger mammals."

Zapol adds, "It could be that inhaled hydrogen sulfide will
only be useful in small animals and we'll need to use intravenous
drugs that can deliver hydrogen sulfide to vital organs to prevent
lung toxicity in larger animals." Zapol is the Reginald Jenney
Professor of Anaesthesia at Harvard Medical School.

The study was supported by grants from the National Institutes
of Health and Linde Gas Therapeutics. Additional co-authors of the
Anesthesiology report are Robert Searles, Binglan Yu, PhD,
Fumito Ichinose, MD, and Kenneth Bloch, MD, MGH Anesthesia; and
Marielle Scherrer-Crosbie, MD, MGH Cardiology.

Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.